Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, randomized controlled trial was designed to test whether the monoclonal antibody rituximab is non-inferior to steroids in maintaining remission in juvenile forms of SDNS and how long remission may last (EudraCT:2008-004486-26).
We enrolled 30 children 4–15 years who had developed SDNS 6–12 months before and were maintained in remission with low prednisone doses (0.1–0.4 mg/Kg/day). Participants were randomized following a non-inferiority design to continue prednisone alone (n 15, controls) or to add a single intravenous infusion of rituximab (375 mg/m2, n 15 intervention). Prednisone was tapered in both arms after 1 month. Children assigned to the control arm were allowed to receive rituximab to treat disease relapse.
Proteinuria increased at 3 months in the prednisone group (from 0.14 to 1.5 g/day) (p < 0.001) and remained unchanged in the rituximab group (0.14 g/day). Fourteen children in the control arm relapsed within 6 months. Thirteen children assigned to rituximab (87%) were still in remission at 1 year and 8 (53%) at 4 years. Responses were similar in children of the control group who received rituximab to treat disease relapse. We did not record significant adverse events.
Rituximab was non-inferior to steroids for the treatment of juvenile SDNS. One in two children remains in remission at 4 years following a single infusion of rituximab, without significant adverse events. Further studies are needed to clarify the superiority of rituximab over low-dose corticosteroid as a treatment of SDNS.
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This study was supported by Istituto Giannina Gaslini deriving from ‘Cinque per mille of IRPEF-Finanziamento della ricerca sanitaria’, the Italian Ministry of Health, The Renal Child Foundation, and the ‘Fondazione La Nuova Speranza’ (‘Progetto integrato per la definizione dei meccanismi implicati nella glomerulosclerosi focale’). GMG received a grant from Compagnia San Paolo (ROL-9849).
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Ravani, P., Lugani, F., Pisani, I. et al. Rituximab for very low dose steroid-dependent nephrotic syndrome in children: a randomized controlled study. Pediatr Nephrol 35, 1437–1444 (2020). https://doi.org/10.1007/s00467-020-04540-4
- Paediatric nephrology
- Steroid-dependent nephrotic syndrome